The protective effect of ginsenoside Rg1 against sepsis-induced lung injury through PI3K-Akt pathway: insights from molecular dynamics simulation and experimental validation.

Sepsis-induced acute lung injury (SALI) poses a significant threat with high incidence and mortality rates. Ginsenoside Rg1 (GRg1), derived from Ginseng in traditional Chinese medicine, has been found to reduce inflammation and protect lung epithelial cells against tissue damage. However, the specific roles and mechanisms by which GRg1 mitigates SALI have yet to be fully elucidated. In this context, we employed a relevant SALI mouse model, alongside network pharmacology, molecular docking, and molecular dynamics simulation to pinpoint GRg1's action targets, complemented by in vitro assays to explore the underlying mechanisms. Our research shows that GRg1 alleviates CLP-induced SALI, decreasing lung tissue damage and levels of serum proinflammatory factor IL-6, TNF-α, and IL-1ß, also enhancing the survival rate of CLP mice. A total of 116 common targets between GRg1 and ALI, with specific core targets including AKT1, VEGFA, SRC, IGF1, ESR1, STAT3, and ALB. Further in vitro experiments assessed GRg1's intervention effects on MLE-12 cells exposed to LPS, with qRT-PCR analysis and molecular dynamics simulations confirming AKT1 as the key target with the favorable binding activity for GRg1. Western blot results indicated that GRg1 increased the Bcl-2/Bax protein expression ratio to reduce apoptosis and decreased the high expression of cleaved caspase-3 in LPS-induced MLE-12 cells. More results showed significant increases in the phosphorylation of PI3K and AKT1. Flow cytometric analysis using PI and Annexin-V assays further verified that GRg1 decreased the apoptosis rate in LPS-stimulated MLE-12 cells (from 14.85 to 6.54%, p < 0.05). The employment of the AKT1 inhibitor LY294002 confirmed these trends, indicating that AKT1's inhibition negates GRg1's protective effects on LPS-stimulated MLE-12 cells. In conclusion, our research highlights GRg1's potential as an effective adjunct therapy for SALI, primarily by inhibiting apoptosis in alveolar epithelial cells and reducing pro-inflammatory cytokine secretion, thus significantly enhancing the survival rates of CLP mice. These beneficial effects are mediated through targeting AKT1 and activating the PI3K-AKT pathway.

[Isolation and identification of malonyl ginsenoside-Ra_1 and malonyl ginsenoside-Ra_2 from fresh roots of Panax ginseng].

The aim of this paper is to study the malonyl ginsenosides in the fresh roots of Panax ginseng. D101 macroporous adsorption resin, ODS, and preparative HPLC were employed to separate the chemical components from the 70% ethanol extract of the fresh roots of P. ginseng, and the structures of the separated compounds were identified based on the data of high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Two malonyl ginsenosides were isolated from the fresh roots of P. ginseng and identified as 3-O-\[6-O-malonyl-ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosyl\]-20-O-\[ ß-D-xylopyranosyl-(1→4)-α-L-arabinopyranosyl-(1→6)-ß-D-glucopyranosyl\]-dammar-24-ene-3ß,12ß,20S-triol(1) and 3-O-\[6-O-malonyl-ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosyl\]-20-O-\[ ß-D-xylopyranosyl-(1→2)-α-L-arabinofuranosyl-(1→6)-ß-D-glucopyranosyl\]-dammar-24-ene-3ß,12ß,20S-triol(2), respectively. Compounds 1 and 2 are new compounds isolated from fresh roots of P. ginseng for the first time and named as malonyl ginsenoside-Ra_1 and malonyl ginsenoside-Ra_2, respectively.

Evaluation and comparison of liquid chromatography/high-resolution mass spectrometry platforms for the separation and characterization of ginsenosides from the leaves of Panax ginseng.

The measurement of data repeatability in small-molecule metabolites acquired within and among different liquid chromatography-mass spectrometry (LC-MS) platforms is crucial for data sharing or data transfer in natural products research. This work was designed to investigate and evaluate the separation and detection performance of three commercial high-resolution LC-MS platforms (e.g., Agilent 6550 QTOF, Waters Vion IM-QTOF, and Thermo Scientific Orbitrap Exploris 120) using 68 ginsenoside references and the extract of Panax ginseng leaf. The retention time (tR), measured on these three platforms (under the same chromatography condition), showed good stability in different concentration tests, and within/among different instruments for both intra-day and inter-day precision examinations. Correlation in tR of ginsenosides was also highly determined on these three platforms. In spite of the different mass analyzers involved, these three platforms gave the accurate mass determination ability, especially enhanced resolution gained because of the ion mobility (IM) separation facilitated by IM-quadrupole time-of-flight. The current study has systematically evaluated the separation and MS detection performance enabled by three high-resolution LC-MS platforms taking ginsenosides as the template, and the reported findings can benefit the researchers for the selection of analytical platforms and the purpose of data sharing or data transfer.

A pH-triggered N-oxide polyzwitterionic nano-drug loaded system for the anti-tumor immunity activation research.

Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.

Increasing Multienzyme Cascade Efficiency and Stability of MOF via Partitioning Immobilization.

Enhancing the stability of multienzyme cascade reactions in metal-organic frameworks (MOFs) is a challenging task in the fields of biotechnology and chemistry. However, addressing this challenge could yield far-reaching benefits across the application range in the biomedical, food, and environmental sectors. In this study, multienzyme partitioning immobilization that sequentially immobilizes cascade enzymes with hierarchical MOFs is proposed to reduce substrate diffusion resistance. Conversion results of ginsenosides indicate that this strategy improves the cascade efficiency up to 1.26 times. The substrate diffusion model is used to investigate the dual-interenzyme mass transfer behavior of substrates in the restricted domain space and evaluate the substrate channeling effect under partitioning immobilization. Molecular docking and kinetic simulations reveal that the MOFs effectively limit the conformational changes of cascade enzymes at high temperatures and in organic solvents while maintaining a large pocket of active centers. This phenomenon increased efficient substrate docking to the enzyme molecules, further optimizing cascade efficiency. The results of the immobilization of GOX and horseradish peroxidase as model enzymes indicate that the partitioned MOF immobilization strategy could be used for universal adaptation of cascade enzymes.

Molecularly imprinted polymer-coated silica microbeads for high-performance liquid chromatography.

Molecularly imprinted polymer (MIP)-based chromatographic separation materials, owing to their advantages of unique selectivity, low cost, suitable reproducibility, and acceptable stability, have attracted a great deal of research in different fields. In this investigation, a new type of MIP-coated silica (MIP/SiO2) separation material was developed using sulfamethoxazole as a template; the specific recognition ability of MIP and appropriate physicochemical properties (abundant Si-OH, suitable pore structure, good stability, etc.) of SiO2 microbeads were combined. The MIP/SiO2 separation materials were characterized carefully. Then, various compounds (such as sulfonamides, ginsenosides, nucleosides, and several pesticides) were used to comprehensively evaluate the chromatographic performances of the MIP/SiO2 column. Furthermore, the chromatographic performances of the MIP/SiO2 column were compared with those of other separation materials (such as non-imprinted polymer-coated silica, C18/SiO2, and bare silica) packed columns. The resolution value of all measured compounds was more than 1.51. The column efficiencies of 13 510 plates per meter (N m-1) for sulfamethoxazole, 11 600 N m-1 for ginsenoside Rd, and 10 510 N m-1 for 2'-deoxyadenosine were obtained. The acceptable results verified that the MIP/SiO2 column can be applied to separate highly polar drugs such as sulfonamides, ginsenosides, nucleosides, and pesticides.

Self-Assembled Micelles Based on Ginsenoside Rg5 for the Targeted Treatment of PTX-Resistant Tumors.

Paclitaxel (PTX) is one of the first-line drugs for prostate cancer (PC) treatment. However, the poor water solubility, inadequate specific targeting ability, multidrug resistance, and severe neurotoxicity are far from being fully resolved, despite diverse PTX formulations in the market, such as the gold-standard PTX albumin nanoparticle (Abraxane) and polymer micelles (Genexol-PM). Some studies attempting to solve the multiple problems of chemotherapy delivery fall into the trap of an extremely complicated formulation design and sacrifice druggability. To better address these issues, this study designed an efficient, toxicity-reduced paclitaxel-ginsenoside polymeric micelle (RPM). With the aid of the inherent amphiphilic molecular structure and pharmacological effects of ginsenoside Rg5, the prepared RPM enhances the water solubility and active targeting of PTX, inhibiting chemotherapy resistance in cancer cells. Moreover, the polymeric micelles demonstrated favorable anti-inflammatory and neuroprotective effects, providing ideas for the development of new clinical anti-PC preparations.

A ginsenoside G-Rg3 PEGylated long-circulating liposome for hyperglycemia and insulin resistance therapy in streptozotocin-induced type 2 diabetes mice.

Ginsenoside (GS), one of the main active components in ginseng, can enhance insulin sensitivity, improve the function of islet ß cells, and reduce cell apoptosis in the treatment of diabetes. However, the drawbacks of high lipid solubility, poor water solubility, and low oral availability in Ginsenoside Rg3 (G-Rg3) seriously limit further application of GS. In this work, a G-Rg3 PEGylated long-circulating liposome (PEG-L-Rg3) is designed and developed to improve symptoms in type 2 diabetic mice. The as-prepared PEG-L-Rg3 with a spherical structure shows a particle size of âˆ¼ 140.5 ± 1.4 nm, the zeta potential of -0.10 ± 0.05 mV, and a high encapsulation rate of 99.8 %. Notably, in vivo experimental results demonstrate that PEG-L-Rg3 exhibits efficient ability to improve body weight and food intake in streptozotocin-induced type 2 diabetic mice. Moreover, PEG-L-Rg3 also enhances fasting insulin (FINS) and insulin sensitivity index (ISI). In addition, the glucose tolerance of mice is significantly improved after the treatment of PEG-L-Rg3, indicating that PEG-L-Rg3 can be a potential drug for the treatment of type 2 diabetes, which provides a new way for the treatment of type 2 diabetes using ginsenosides.

Characterization of a glycosyltransferase from Paris polyphylla for application in biosynthesis of rare ophiopogonins and ginsenosides.

Saponins are bioactive components of many medicinal plants, possessing complicated chemical structures and extensive pharmacological activities, but the production of high-value saponins remains challenging. In this study, a 6'-O-glucosyltransferase PpUGT7 (PpUGT91AH7) was functionally characterized from Paris polyphylla Smith var. yunnanensis (Franch.) Hand. -Mazz., which can transfer a glucosyl group to the C-6' position of diosgenin-3-O-rhamnosyl-(1 â†’ 2)-glucoside (1), pennogenin-3-O-rhamnosyl-(1 â†’ 2)-glucoside (2), and diosgenin-3-O-glucoside (5). The KM and Kcat values of PpUGT7 towards the substrate 2 were 8.4 µM and 2 × 10-3 s-1, respectively. Through molecular docking and site-directed mutagenesis, eight residues were identified to interact with the sugar acceptor 2 and be crucial for enzyme activity. Moreover, four rare ophiopogonins and ginsenosides were obtained by combinatorial biosynthesis, including an undescribed compound ruscogenin-3-O-glucosyl-(1 â†’ 6)-glucoside (10). Firstly, two monoglycosides 9 and 11 were generated using a known sterol 3-O-ß-glucosyltransferase PpUGT80A40 with ruscogenin (7) and 20(S)-protopanaxadiol (8) as substrates, which were further glycosylated to the corresponding diglycosides 10 and 12 under the catalysis of PpUGT7. In addition, compounds 7-11 were found to show inhibitory effects on the secretion of TNF-α and IL-6 in macrophages RAW264.7. The findings provide valuable insights into the enzymatic glycosylation processes in the biosynthesis of bioactive saponins in P. polyphylla var. yunnanensis, and also serve as a reference for utilizing UDP-glycosyltransferases to construct high-value or rare saponins for development of new therapeutic agents.

Targeted Delivery of Macrophage Membrane Biomimetic Liposomes Through Intranasal Administration for Treatment of Ischemic Stroke.

Purpose: Ginsenoside Rg3 (Rg3) and Panax notoginseng saponins (PNS) can be used for ischemic stroke treatment, however, the lack of targeting to the ischemic region limits the therapeutic effect. To address this, we leveraged the affinity of macrophage membrane proteins for inflamed brain microvascular endothelial cells to develop a macrophage membrane-cloaked liposome loaded with Rg3 and PNS (MM-Lip-Rg3/PNS), which can precisely target brain lesion region through intranasal administration. Methods: MM-Lip-Rg3/PNS was prepared by co-extrusion method and was performed by characterization, stability, surface protein, and morphology. The cellular uptake, immune escape ability, and blood-brain barrier crossing ability of MM-Lip-Rg3/PNS were studied in vitro. The in vivo brain targeting, biodistribution and anti-ischemic efficacy of MM-Lip-Rg3/PNS were evaluated in MACO rats, and we determined the diversity of the nasal brain pathway through the olfactory nerve blockade model in rats. Finally, the pharmacokinetics and brain targeting index of MM-Lip-Rg3/PNS were investigated. Results: Our results indicated that MM-Lip-Rg3/PNS was spherical with a shell-core structure. MM-Lip-Rg3/PNS can avoid mononuclear phagocytosis, actively bind to inflammatory endothelial cells, and have the ability to cross the blood-brain barrier. Moreover, MM-Lip-Rg3/PNS could specifically target ischemic sites, even microglia, increase the cumulative number of drugs in the brain, improve the inflammatory environment of the brain, and reduce the infarct size. By comparing olfactory nerve-blocking rats with normal rats, it was found that there are direct and indirect pathways for nasal entry into the brain. Pharmacokinetics demonstrated that MM-Lip-Rg3/PNS exhibited stronger brain targeting and prolonged drug half-life. Conclusion: MM-Lip-Rg3/PNS might contribute to the accumulation of Rg3 and PNS in the ischemic brain area to improve treatment efficacy. This biomimetic nano-drug delivery system provides a new and promising strategy for the treatment of ischemic stroke.

In Vitro Investigations into the Potential Drug Interactions of Pseudoginsenoside DQ Mediated by Cytochrome P450 and Human Drug Transporters.

Pseudoginsenoside DQ (PDQ), an ocotillol-type ginsenoside, is synthesized with protopanaxadiol through oxidative cyclization. PDQ exhibits good anti-arrhythmia activity. However, the inhibitory effect of PDQ on the cytochrome 450 (CYP450) enzymes and major drug transporters is still unclear. Inhibition of CYP450 and drug transporters may affect the efficacy of the drugs being used together with PDQ. These potential drug-drug interactions (DDIs) are essential for the clinical usage of drugs. In this study, we investigated the inhibitory effect of PDQ on seven CYP450 enzymes and seven drug transporters with in vitro models. PDQ has a significant inhibitory effect on CYP2C19 and P-glycoprotein (P-gp) with a half-inhibitory concentration (IC50) of 0.698 and 0.41 µM, respectively. The inhibition of CYP3A4 and breast cancer-resistant protein (BCRP) is less potent, with IC50 equal to 2.02-6.79 and 1.08 µM, respectively.

A versatile economic strategy by HPLC-CAD for quantification of structurally diverse markers in quality control of Shengmai Formula from raw materials to preparations.

BACKGROUND: Shengmai Formula (SMF), a classic formula in treating Qi-Yin deficiency, is composed of Ginseng Radix et Rhizoma Rubra (GRR), Ophiopogon Radix (OR), and Schisandra chinensis Fructus (SC), and has been developed into various dosage forms including Shengmai Yin Oral Liquid (SMY), Shengmai Capsules (SMC), and Shengmai Injection (SMI). The pharmacological effects of compound Chinese medicine are attributed to the integration of multiple components. Yet the quality criteria of SMF are limited to monitoring schisandrol A or ginsenosides Rg1 and Re, but none for OR. Since the complexity of raw materials and preparations, establishing a economical and unified method for SMF is challenging. It is urgent to simultaneously quantify multiple components with different structures using a universal method for quality control of SMF. Charged aerosol detector (CAD) overcame the above shortcomings owing to its characteristics of high responsiveness, nondiscrimination, and low cost. PURPOSE: We aimed to establish a versatile analysis strategy using HPLC-CAD for simultaneously quantifying the structurally diverse markers in quality control of SMF from raw materials to preparations. METHOD: By optimizing the column, mobile phase, column temperature, flow rate, and CAD parameters, a HPLC-CAD method that integrated multi-component characterization, authenticity identification, transfer information of raw materials and quantitative determination of Shengmai preparations was established. RESULTS: In total 50 components from SMF were characterized (28 in GRR, 13 in SC, and 9 in OR). The differences in raw materials between species of SC and Schisandrae sphenantherae Fructus (SS), processing methods of Ginseng Radix (GR) and GRR, and locations of OR from Sichuan (ORS) and Zhejiang (ORZ) were compared. Fourteen components in 19 batches of SMY, SMC and SMI from different manufacturers were quantified, including 11 ginsenosides and 3 lignans. The multivariate statistical analysis results further suggested that Rb1, Rg1 and Ro were the main differences among Shengmai preparations. CONCLUSION: The established versatile analysis strategy based on HPLC-CAD was proven sensitive, simple, convenient, overcoming the discriminatory effect of UV detector, revealing the composition and transfer information of SMF and applicable for authentication of the ingredient herbs and improving the quality of Shengmai preparations.

Synergistic promotion of angiogenesis after intracerebral hemorrhage by ginsenoside Rh2 and chrysophanol in rats.

BACKGROUND: Intracerebral hemorrhage (ICH) is a debilitating condition characterized by the rupture of cerebral blood vessels, resulting in profound neurological deficits. A significant challenge in the treatment of ICH lies in the brain's limited capacity to regenerate damaged blood vessels. This study explores the potential synergistic effects of Ginsenoside Rh2 and Chrysophanol in promoting angiogenesis following ICH in a rat model. METHODS: Network pharmacology was employed to predict the potential targets and pathways of Ginsenoside Rh2 and Chrysophanol for ICH treatment. Molecular docking was utilized to assess the binding affinity between these compounds and their respective targets. Experimental ICH was induced in male Sprague-Dawley rats through stereotactic injection of type VII collagenase into the right caudate putamen (CPu). The study encompassed various methodologies, including administration protocols, assessments of neurological function, magnetic resonance imaging, histological examination, observation of brain tissue ultrastructure, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunofluorescence staining, Western blot analysis, and statistical analyses. RESULTS: Network pharmacology analysis indicated that Ginsenoside Rh2 and Chrysophanol may exert their therapeutic effects in ICH by promoting angiogenesis. Results from animal experiments revealed that rats treated with Ginsenoside Rh2 and Chrysophanol exhibited significantly improved neurological function, reduced hematoma volume, and diminished pathological injury compared to the Model group. Immunofluorescence analysis demonstrated enhanced expression of vascular endothelial growth factor receptor 2 (VEGFR2) and CD31, signifying augmented angiogenesis in the peri-hematomal region following combination therapy. Importantly, the addition of a VEGFR2 inhibitor reversed the increased expression of VEGFR2 and CD31. Furthermore, Western blot analysis revealed upregulated expression of angiogenesis-related factors, including VEGFR2, SRC, AKT1, MAPK1, and MAPK14, in the combination therapy group, but this effect was abrogated upon VEGFR2 inhibitor administration. CONCLUSION: The synergistic effect of Ginsenoside Rh2 and Chrysophanol demonstrated a notable protective impact on ICH injury in rats, specifically attributed to their facilitation of angiogenesis. Consequently, this research offers a foundation for the utilization of Ginsenosides Rh2 and Chrysophanol in medical settings and offers direction for the advancement of novel pharmaceuticals for the clinical management of ICH.

Target Cell Extraction and Spectrum-Effect Relationship Coupled with BP Neural Network Classification for Screening Potential Bioactive Components in Ginseng Extract with a Protective Effect against Myocardial Damage.

Cardiovascular disease has become a common ailment that endangers human health, having garnered widespread attention due to its high prevalence, recurrence rate, and sudden death risk. Ginseng possesses functions such as invigorating vital energy, enhancing vein recovery, promoting body fluid and blood nourishment, calming the nerves, and improving cognitive function. It is widely utilized in the treatment of various heart conditions, including palpitations, chest pain, heart failure, and other ailments. Although numerous research reports have investigated the cardiovascular activity of single ginsenoside, there remains a lack of systematic research on the specific components group that predominantly contribute to cardiovascular efficacy in ginseng medicinal materials. In this research, the spectrum-effect relationship, target cell extraction, and BP neural network classification were used to establish a rapid screening system for potential active substances. The results show that red ginseng extract (RGE) can improve the decrease in cell viability and ATP content and inhibit the increase in ROS production and LDH release in OGD-induced H9c2 cells. A total of 70 ginsenosides were identified in RGE using HPLC-Q-TOF-MS/MS analysis. Chromatographic fingerprints were established for 12 batches of RGE by high-performance liquid chromatography (HPLC). A total of 36 common ingredients were found in 12 batches of RGE. The cell viability, ATP, ROS, and LDH of 12 batches RGE were tested to establish gray relationship analysis (GRA) and partial least squares discrimination analysis (PLS-DA). BP neural network classification and target cell extraction were used to narrow down the scope of Spectral efficiency analysis and screen the potential active components. According to the cell experiments, RGE can improve the cell viability and ATP content and reduce the oxidative damage. Then, seven active ingredients, namely, Ginsenoside Rg1, Rg2, Rg3, Rb1, Rd, Re, and Ro, were screened out, and their cardiovascular activity was confirmed in the OGD model. The seven ginsenosides were the main active substances of red ginseng in treating myocardial injury. This study offers a reference for quality control in red ginseng and preparations containing red ginseng for the management of cardiovascular diseases. It also provides ideas for screening active ingredients of the same type of multi-pharmacologically active traditional Chinese medicines.

3D printing of Rg3-loaded hydrogel scaffolds: anti-inflammatory and scar-formation related collagen inhibitory effects for scar-free wound healing.

During the process of wound healing, the stimulation of inflammatory factors often leads to abnormal proliferation of blood vessels and collagen, ultimately resulting in scar formation. To address this challenge, we fabricate a novel dermal extracellular matrix (DECM) hydrogel scaffold loaded with ginsenoside Rg3 (Rg3) using 3D printing technology. Mesoporous silica nanoparticles (MSNs) are introduced into the system to encase the Rg3 to control its release rate and enhance its bioavailability. We systematically evaluate the biological, physicochemical, and wound healing properties of this scaffold. In vitro studies demonstrate that the hydrogel exhibits excellent biocompatibility and solid-like rheological properties, ensuring its successful printing. In vivo studies reveal that the composite hydrogel scaffolds effectively accelerate wound healing and achieve scar-free wound healing within three weeks. Histological and immunohistochemical (IHC) analyses show that the composite hydrogel scaffolds reduce the inflammatory response and inhibit excessive collagen accumulation. These combined effects underscore the potential of our approach in effectively inhibiting scar formation.

Bioinspired ginsenoside Rg3 PLGA nanoparticles coated with tumor-derived microvesicles to improve chemotherapy efficacy and alleviate toxicity.

Breast cancer, a pervasive malignancy affecting women, demands a diverse treatment approach including chemotherapy, radiotherapy, and surgical interventions. However, the effectiveness of doxorubicin (DOX), a cornerstone in breast cancer therapy, is limited when used as a monotherapy, and concerns about cardiotoxicity persist. Ginsenoside Rg3, a classic compound of traditional Chinese medicine found in Panax ginseng C. A. Mey., possesses diverse pharmacological properties, including cardiovascular protection, immune modulation, and anticancer effects. Ginsenoside Rg3 is considered a promising candidate for enhancing cancer treatment when combined with chemotherapy agents. Nevertheless, the intrinsic challenges of Rg3, such as its poor water solubility and low oral bioavailability, necessitate innovative solutions. Herein, we developed Rg3-PLGA@TMVs by encapsulating Rg3 within PLGA nanoparticles (Rg3-PLGA) and coating them with membranes derived from tumor cell-derived microvesicles (TMVs). Rg3-PLGA@TMVs displayed an array of favorable advantages, including controlled release, prolonged storage stability, high drug loading efficiency and a remarkable ability to activate dendritic cells in vitro. This activation is evident through the augmentation of CD86+CD80+ dendritic cells, along with a reduction in phagocytic activity and acid phosphatase levels. When combined with DOX, the synergistic effect of Rg3-PLGA@TMVs significantly inhibits 4T1 tumor growth and fosters the development of antitumor immunity in tumor-bearing mice. Most notably, this delivery system effectively mitigates the toxic side effects of DOX, particularly those affecting the heart. Overall, Rg3-PLGA@TMVs provide a novel strategy to enhance the efficacy of DOX while simultaneously mitigating its associated toxicities and demonstrate promising potential for the combined chemo-immunotherapy of breast cancer.

Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

Preparation of pH-sensitive carboxymethyl chitosan nanoparticles loaded with ginsenoside Rb1 and evaluation of drug release in vitro.

Oral absorption of ginsenoside Rb1 (Rb1) is often hindered by the gastrointestinal tract. Carboxymethyl chitosan deoxycholic acid loaded with ginsenoside Rb1 nanoparticles (CMDA@Rb1-NPs), were prepared as a delivery system using a self-assembly technique with amphipathic deoxycholic acid grafted carboxymethyl chitosan as the carrier, which improved the stability and embedding rate of Rb1. In addition, the CMDA@Rb1-NPs was encapsulated with sodium alginate by ion crosslinking method with additional layer (CMDAlg@Rb1-NPs). Scanning electron microscopy showed that the nanoparticles were spherical, evenly distributed, smooth and without obvious adhesion. By evaluating drug loading, entrapment efficiency, the encapsulation efficiency of Rb1 increased from 60.07 % to 72.14 % after grafting deoxycholic acid improvement and optimization. In vitro release results showed that the cumulative release of Rb1 by CMDAlg-NPs showed a pH dependent effect, which was <10 % in simulated gastric juice with pH 1.2, completely released with pH 7.4 for about 48 h. In addition, Rb1 and CMDAlg@Rb1-NPs had inhibitory effects on A549 cells, and the inhibitory effect of CMDAlg@Rb1-NPs was better. Therefore, all results indicated that CMDA/Alg@Rb1 nanoparticles might be a novel drug delivery system to improve the stability and embedding rate of Rb1, and has the potential to be applied in oral pharmaceutical preparations.

Changes in chemical components and hepatoprotective effect of red Panax notoginseng processed by aspartic acid impregnation treatment.

BACKGROUND: Red Panax notoginseng (RPN) is one of the major processed products of P. notoginseng (PN), with more effective biological activities. However, the traditional processing method of RPN has some disadvantages, such as low conversion rate of ginsenosides and long processing time. RESULTS: In this work, we developed a green, safe, and efficient approach for RPN processing by aspartic acid impregnation pretreatment. Our results showed that the optimized temperature, steaming time, and concentration of aspartic acid were 120 °C, 1 h, and 3% respectively. The original ginsenosides in PN treated by aspartic acid (Asp-PN) were completely converted to rare saponins at 120 °C within just 1 h. The concentration of the rare ginsenosides in Asp-PN was two times higher than that in untreated RPN. In addition, we examined the protective effect of RPN and Asp-PN on acetaminophen-induced liver injury in a mouse model. The results showed that Asp-PN has significantly more potent hepatoprotective action than the RPN. The hepatoprotection of Asp-PN in acetaminophen-induced hepatotoxicity may be due to its anti-oxidative stress, anti-apoptotic, and anti-inflammatory activities. CONCLUSION: These results indicated that aspartic acid impregnation pretreatment may provide an effective method to shorten the steaming time, improve the conversion rate of ginsenosides, and enhance hepatoprotective activity of RPN. © 2024 Society of Chemical Industry.

Ginsenoside Rg3: A Review of its Anticancer Mechanisms and Potential Therapeutic Applications.

BACKGROUND: Traditional Chinese Medicine (TCM) has a long history of treating various diseases and is increasingly being recognized as a complementary therapy for cancer. A promising natural compound extracted from the Chinese herb ginseng is ginsenoside Rg3, which has demonstrated significant anticancer effects. It has been tested in a variety of cancers and tumors and has proven to be effective in suppressing cancer. OBJECTIVES: This work covers various aspects of the role of ginsenoside Rg3 in cancer treatment, including its biological functions, key pathways, epigenetics, and potential for combination therapies, all of which have been extensively researched and elucidated. The study aims to provide a reference for future research on ginsenoside Rg3 as an anticancer agent and a support for the potential application of ginsenoside Rg3 in cancer treatment.